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Article ; Online: Whole Cell Patch Clamp Electrophysiology in Human Neuronal Cells.

Gabriel, Rafael / Boreland, Andrew J / Pang, Zhiping P

Methods in molecular biology (Clifton, N.J.)

2023 Volume 2683, Page(s) 259–273

Abstract: Whole cell patch clamp recording techniques are commonly used to assay membrane excitability, ion channel function, and synaptic activity in neurons. However, assaying these functional properties of human neurons remains difficult because of the ... ...

Abstract	Whole cell patch clamp recording techniques are commonly used to assay membrane excitability, ion channel function, and synaptic activity in neurons. However, assaying these functional properties of human neurons remains difficult because of the difficulty in obtaining human neuronal cells. Recent advents in stem cell biology, especially the development of the induced pluripotent stem cells, made it possible to generate human neuronal cells in both 2-dimensional (2D) monolayer cultures and 3D brain-organoid cultures. Here, we describe the whole cell patch clamp methods of recording neuronal physiology from human neuronal cells.
MeSH term(s)	Humans ; Neurons/metabolism ; Electrophysiological Phenomena ; Induced Pluripotent Stem Cells ; Brain ; Electrophysiology
Language	English
Publishing date	2023-06-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-3287-1_21
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Dorsolateral septum GLP-1R neurons regulate feeding via lateral hypothalamic projections.

Lu, Yi / Wang, Le / Luo, Fang / Savani, Rohan / Rossi, Mark A / Pang, Zhiping P

bioRxiv : the preprint server for biology

2024

Abstract: Objective: Although glucagon-like peptide 1 (GLP-1) is known to regulate feeding, the central mechanisms contributing to this function remain enigmatic. Here, we aim to test the role of neurons expressing GLP-1 receptors (GLP-1R) in the dorsolateral ... ...

Abstract	Objective: Although glucagon-like peptide 1 (GLP-1) is known to regulate feeding, the central mechanisms contributing to this function remain enigmatic. Here, we aim to test the role of neurons expressing GLP-1 receptors (GLP-1R) in the dorsolateral septum (dLS; dLS Methods: Using chemogenetic manipulations, we assessed how activation or inhibition of dLS Results: Chemogenetic inhibition of dLS Conclusions: Together, these results demonstrate that dLS-GLP-1R neurons and the inhibitory pathway to LHA can regulate feeding behavior, which might serve as a potential therapeutic target for the treatment of eating disorders or obesity. Highlights: Chemogenetic inhibition of dLS
Language	English
Publishing date	2024-03-27
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.03.26.586855
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Article ; Online: Hypothalamic melanin-concentrating hormone regulates hippocampus-dorsolateral septum activity.

Liu, Jing-Jing / Tsien, Richard W / Pang, Zhiping P

Nature neuroscience

2022 Volume 25, Issue 1, Page(s) 61–71

Abstract: Hypothalamic melanin-concentrating hormone (MCH) polypeptide contributes to regulating energy homeostasis, sleep and memory, although the mechanistic bases of its effects are unknown. In this study, in mice, we uncovered the physiological mechanism ... ...

Abstract	Hypothalamic melanin-concentrating hormone (MCH) polypeptide contributes to regulating energy homeostasis, sleep and memory, although the mechanistic bases of its effects are unknown. In this study, in mice, we uncovered the physiological mechanism underlying the functional role of MCH signaling in projections to the dorsolateral septum (dLS), a region involved in routing hippocampal firing rhythms and encoding spatial memory based on such rhythms. Firing activity within the dLS in response to dorsal CA3 (dCA3) excitation is limited by strong feed-forward inhibition (FFI). We found that MCH synchronizes dLS neuronal firing with its dCA3 inputs by enhancing GABA release, which subsequently reduces the FFI and augments dCA3 excitatory input strength, both via pre-synaptic mechanisms. At the functional level, our data reveal a role for MCH signaling in the dLS in facilitating spatial memory. These findings support a model in which peptidergic signaling within the dLS modulates dorsal hippocampal output and supports memory encoding.
MeSH term(s)	Animals ; Hippocampus/physiology ; Hypothalamic Hormones/metabolism ; Melanins ; Mice ; Pituitary Hormones
Chemical Substances	Hypothalamic Hormones ; Melanins ; Pituitary Hormones ; melanin-concentrating hormone (67382-96-1)
Language	English
Publishing date	2022-01-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1420596-8
ISSN	1546-1726 ; 1097-6256
ISSN (online)	1546-1726
ISSN	1097-6256
DOI	10.1038/s41593-021-00984-5
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Zs.A 4891: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 67: Show issues

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Article ; Online: Sustained type I interferon signaling after human immunodeficiency virus type 1 infection of human iPSC derived microglia and cerebral organoids.

Boreland, Andrew J / Stillitano, Alessandro C / Lin, Hsin-Ching / Abbo, Yara / Hart, Ronald P / Jiang, Peng / Pang, Zhiping P / Rabson, Arnold B

iScience

2024 Volume 27, Issue 5, Page(s) 109628

Abstract: Human immunodeficiency virus type-1 (HIV-1)-associated neurocognitive disorder (HAND) affects up to half of people living with HIV-1 and causes long term neurological consequences. The pathophysiology of HIV-1-induced glial and neuronal functional ... ...

Abstract	Human immunodeficiency virus type-1 (HIV-1)-associated neurocognitive disorder (HAND) affects up to half of people living with HIV-1 and causes long term neurological consequences. The pathophysiology of HIV-1-induced glial and neuronal functional deficits in humans remains enigmatic. To bridge this gap, we established a model simulating HIV-1 infection in the central nervous system using human induced pluripotent stem cell (iPSC)-derived microglia combined with sliced neocortical organoids. Incubation of microglia with two replication-competent macrophage-tropic HIV-1 strains (JRFL and YU2) elicited productive infection and inflammatory activation. RNA sequencing revealed significant and sustained activation of type I interferon signaling pathways. Incorporating microglia into sliced neocortical organoids extended the effects of aberrant type I interferon signaling in a human neural context. Collectively, our results illuminate a role for persistent type I interferon signaling in HIV-1-infected microglia in a human neural model, suggesting its potential significance in the pathogenesis of HAND.
Language	English
Publishing date	2024-03-28
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2024.109628
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Article ; Online: CASK

McSweeney, Danny / Gabriel, Rafael / Jin, Kang / Pang, Zhiping P / Aronow, Bruce / Pak, ChangHui

iScience

2022 Volume 25, Issue 10, Page(s) 105187

Abstract: Loss-of-function (LOF) mutations ... ...

Abstract	Loss-of-function (LOF) mutations in
Language	English
Publishing date	2022-09-23
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2022.105187
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Article: Metabolic and behavioral alterations associated with viral vector-mediated toxicity in the paraventricular hypothalamic nucleus.

Savani, Rohan / Park, Erin / Busannagari, Nidhi / Lu, Yi / Kwon, Hyokjoon / Wang, Le / Pang, Zhiping P

bioRxiv : the preprint server for biology

2024

Abstract: Objective: Combining adeno-associated virus (AAV)-mediated expression of Cre recombinase with genetically modified floxed animals is a powerful approach for assaying the functional role of genes in regulating behavior and metabolism. Extensive research ... ...

Abstract	Objective: Combining adeno-associated virus (AAV)-mediated expression of Cre recombinase with genetically modified floxed animals is a powerful approach for assaying the functional role of genes in regulating behavior and metabolism. Extensive research in diverse cell types and tissues using AAV-Cre has shown it can save time and avoid developmental compensation as compared to using Cre driver mouse line crossings. We initially sought to study the impact of ablation of corticotropin-releasing hormone (CRH) in the paraventricular hypothalamic nucleus (PVN) using intracranial AAV-Cre injection in adult animals. Methods: In this study, we stereotactically injected AAV8-hSyn-Cre or a control AAV8-hSyn-GFP both Crh-floxed and wild-type mouse PVN to assess behavioral and metabolic impacts. We then used immunohistochemical markers to systematically evaluate the density of hypothalamic peptidergic neurons and glial cells. Results: We found that delivery of one specific preparation of AAV8-hSyn-Cre in the PVN led to the development of obesity, hyperphagia, and anxiety-like behaviors. This effect occurred independent of sex and in both floxed and wild-type mice. We subsequently found that AAV8-hSyn-Cre led to neuronal cell death and gliosis at the site of viral vector injections. These behavioral and metabolic deficits were dependent on injection into the PVN. An alternatively sourced AAV-Cre did not reproduce the same results. Conclusions: Our findings reveal that delivery of a specific batch of AAV-Cre could lead to cellular toxicity and lesions in the PVN that cause robust metabolic and behavioral impacts. These alterations can complicate the interpretation of Cre-mediated gene knockout and highlight the need for rigorous controls.
Language	English
Publishing date	2024-01-05
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.10.26.564009
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Article ; Online: Metabolic and behavioral alterations associated with viral vector-mediated toxicity in the paraventricular hypothalamic nucleus.

Savani, Rohan / Park, Erin / Busannagari, Nidhi / Lu, Yi / Kwon, Hyokjoon / Wang, Le / Pang, Zhiping P

Bioscience reports

2024

Abstract	Objective: Combining adeno-associated virus (AAV)-mediated expression of Cre recombinase with genetically modified floxed animals is a powerful approach for assaying the functional role of genes in regulating behavior and metabolism. Extensive research in diverse cell types and tissues using AAV-Cre has shown it can save time and avoid developmental compensation as compared to using Cre driver mouse line crossings. We initially sought to study the impact of ablation of corticotropin-releasing hormone (CRH) in the paraventricular hypothalamic nucleus (PVN) using intracranial AAV-Cre injection in adult animals. Methods: In this study, we stereotactically injected AAV8-hSyn-Cre or a control AAV8-hSyn-GFP both Crh-floxed and wild-type mouse PVN to assess behavioral and metabolic impacts. We then used immunohistochemical markers to systematically evaluate the density of hypothalamic peptidergic neurons and glial cells. Results: We found that delivery of one specific preparation of AAV8-hSyn-Cre in the PVN led to the development of obesity, hyperphagia, and anxiety-like behaviors. This effect occurred independent of sex and in both floxed and wild-type mice. We subsequently found that AAV8-hSyn-Cre led to neuronal cell death and gliosis at the site of viral vector injections. These behavioral and metabolic deficits were dependent on injection into the PVN. An alternatively sourced AAV-Cre did not reproduce the same results. Conclusions: Our findings reveal that delivery of a specific batch of AAV-Cre could lead to cellular toxicity and lesions in the PVN that cause robust metabolic and behavioral impacts. These alterations can complicate the interpretation of Cre-mediated gene knockout and highlight the need for rigorous controls.
Language	English
Publishing date	2024-01-16
Publishing country	England
Document type	Journal Article
ZDB-ID	764946-0
ISSN	1573-4935 ; 0144-8463
ISSN (online)	1573-4935
ISSN	0144-8463
DOI	10.1042/BSR20231846
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Zs.A 1676: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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Article: State-dependent central synaptic regulation by GLP-1 is essential for energy homeostasis.

Wang, Le / Savani, Rohan / Bernabucci, Matteo / Lu, Yi / Singh, Ishnoor / Xu, Wei / El Ouaamari, Abdelfattah / Wheeler, Michael B / Grill, Harvey J / Rossi, Mark A / Pang, Zhiping P

Research square

2024

Abstract: Central nervous system (CNS) control of metabolism plays a pivotal role in maintaining energy homeostasis. Glucagon-like peptide-1 (GLP-1, encoded ... ...

Abstract	Central nervous system (CNS) control of metabolism plays a pivotal role in maintaining energy homeostasis. Glucagon-like peptide-1 (GLP-1, encoded by
Language	English
Publishing date	2024-03-12
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-3929981/v1
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Article: Loss of the polarity protein Par3 promotes dendritic spine neoteny and enhances learning and memory.

Voglewede, Mikayla M / Ozsen, Elif Naz / Ivak, Noah / Bernabucci, Matteo / Sun, Miao / Pang, Zhiping P / Zhang, Huaye

bioRxiv : the preprint server for biology

2023

Abstract: The Par3 polarity protein is critical for subcellular compartmentalization in different developmental processes. Variants ... ...

Abstract	The Par3 polarity protein is critical for subcellular compartmentalization in different developmental processes. Variants of
Language	English
Publishing date	2023-09-01
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.08.30.555530
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Article: Neuronal connectivity, behavioral, and transcriptional alterations associated with the loss of MARK2.

Caiola, Hanna O / Wu, Qian / Soni, Shaili / Wang, Xue-Feng / Monahan, Kevin / Pang, Zhiping P / Wagner, George C / Zhang, Huaye

bioRxiv : the preprint server for biology

2023

Abstract: Neuronal connectivity is essential for adaptive brain responses and can be modulated by dendritic spine plasticity and the intrinsic excitability of individual neurons. Dysregulation of these processes can lead to aberrant neuronal activity, which has ... ...

Abstract	Neuronal connectivity is essential for adaptive brain responses and can be modulated by dendritic spine plasticity and the intrinsic excitability of individual neurons. Dysregulation of these processes can lead to aberrant neuronal activity, which has been associated with numerous neurological disorders including autism, epilepsy, and Alzheimer's disease. Nonetheless, the molecular mechanisms underlying aberrant neuronal connectivity remains unclear. We previously found that the serine/threonine kinase Microtubule Affinity Regulating Kinase 2 (MARK2), also known as Partitioning Defective 1b (Par1b), is important for the formation of dendritic spines
Language	English
Publishing date	2023-12-07
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.12.05.569759
Database	MEDical Literature Analysis and Retrieval System OnLINE

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